Biology subjects

Fernando, N.

Publications and source records attributed to Fernando, N..

4 recordsLinked to original sources

bioRxiv2025

Magnetic Particle Imaging Lymphography (MPIL): A novel technique for lymph node mapping

During metastasis, tumour cells drain to nearby lymph nodes, the first of which are named the sentinel lymph node(s) (SLN). SLN biopsy (SLNB) determines if metastasis has occurred. Traditionally, SLNB involves injecting a Technetium-labeled tracer peritumourally, pre-operative imaging with SPECT to locate the SLN, and surgery guided by a gamma probe to remove them. Limitations include short tracer half-life which can make scheduling the SLNB difficult, and radiation dose to patients and healthcare workers. Alternatively, magnetic localization, with superparamagnetic iron oxide nanoparticles (SPIONs) as the tracer and a magnetometer to detect SPIONs in the SLN during surgery can be used, however, this lacks pre-operative imaging. Magnetic Particle Imaging (MPI) is a new imaging modality that directly detects SPIONs, holding potential for pre-operative imaging in magnetic SLNB. SPIONs for SLNB should have rapid drainage, high SLN accumulation, and high specificity to the SLN. For MPI Lymphography (MPIL), high particle sensitivity is also important. This study assesses the in vivo pharmacokinetics for SLN mapping with MPIL in a murine model, using five commercially available SPIONs of varying iron core sizes and surface coatings. We show that some SPIONs provide higher MPI signal at the SLN and show the potential to detect higher echelon nodes (HENs). PEGylation of SPIONs and mannose targeted SPIONs increase clearance from the injection site and the mannose targeted SPION reduces flow to HENs.

biophysics↗

bioRxiv2023

Single-cell multiomic analysis reveals the involvement of Type I interferon-responsive CD8+ T cells in amyloid beta-associated memory loss

Alzheimers disease (AD) is the leading cause of dementia worldwide, but there are limited therapeutic options and no current cure. While the involvement of microglia in AD has been highly appreciated, the role of other innate and adaptive immune cells remains largely unknown, partly due to their scarcity and heterogeneity. This study aimed to study non-microglial immune cells in wild type and AD-transgenic mouse brains across different ages. Our results uncovered the presence of a unique CD8+ T cell population that were selectively increased in aging AD mouse brains, here referred to as "disease-associated T cells (DATs)". These DATs were found to express an elevated tissue-resident memory and Type I interferon-responsive gene signature. Further analysis of aged AD mouse brains showed that these CD8+ T cells were not present in peripheral or meningeal tissues. Preventing CD8+ T cell development in AD-transgenic mice via genetic deletion of beta-2 microglobulin (B2m) led to a reduction of amyloid-{beta} plaque formation in aged mice, and improved memory in AD-transgenic mice as early as four months of age. The integration of transcriptomic and epigenomic profiles at the single-cell level revealed potential transcription factors that reshape the regulomes of CD8+ T cells. These findings highlight a critical role for DATs in the progression of AD and provide a new avenue for treatment.

immunology↗

bioRxiv2021

Ion transport modulators differentially modulate inflammatory responses in THP-1 derived macrophages

Ion transport modulators are most commonly used to treat various non-communicable diseases including diabetes and hypertension. They are also known to bind to receptors on various immune cells, but the immunomodulatory properties of most ion transport modulators have not been fully elucidated. We assessed the effects of thirteen FDA approved ion transport modulators namely ambroxol HCl, amiloride HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, omeprazole, pantoprazole, phenytoin, verapamil, drug X and drug Y on superoxide production, nitric oxide production and cytokine expression by THP-1 derived macrophages that had been stimulated with ethanol-inactivated Mycobacterium bovis BCG. Ambroxol HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, pantoprazole, phenytoin, verapamil and drug Y had an inhibitory effect on nitric oxide production, while all the test drugs had an inhibitory effect on superoxide production. Amiloride HCl, diazoxide, digoxin, furosemide, phenytoin, verapamil, drug X and drug Y enhanced the expression of IL-1{beta} and TNF-. Unlike most immunomodulatory compounds currently in clinical use, most of the test drugs inhibited some inflammatory processes while promoting others. Ion pumps and ion channels could therefore serve as targets for more selective immunomodulatory agents which do not cause overt immunosupression.

immunology↗

bioRxiv2018

Dynamic interplay of innate and adaptive immunity during sterile retinal inflammation: Insights from the transcriptome

The pathogenesis of many retinal degenerations, such as age-related macular degeneration (AMD), is punctuated by an ill-defined network of sterile inflammatory responses. The delineation of innate and adaptive immune milieu amongst the broad leukocyte infiltrate, and the gene networks which construct these responses, are poorly described in the eye. Using photo-oxidative damage in a rodent model of subretinal inflammation, we employed a novel RNA-sequencing framework to map the global gene network signature of retinal leukocytes. This revealed a previously uncharted interplay of adaptive immunity during subretinal inflammation, including prolonged enrichment of myeloid and lymphocyte migration, antigen presentation, and the alternative arm of the complement cascade involving Factor B. We demonstrate Factor B-deficient mice are protected against macrophage infiltration and subretinal inflammation. Suppressing the drivers of retinal leukocyte proliferation, or their capacity to elicit complement responses, may help preserve retinal structure and function during sterile inflammation in diseases such as AMD.

neuroscience↗